ACHIEVE LIFE SCIENCES, INC. ORCA-V1 Trial
Ongoing Research of Cytisinicline for Addiction
Cytisinicline for Vaping Cessation Among Adult Nicotine
E-CigaretteUsers: A Multisite Randomized Placebo-Controlled Trial
Nancy Rigotti, MD,1 Neal Benowitz, MD,2 Judith Prochaska, PhD,3 Daniel Cain,4 Julie Ball,4 Anthony Clarke, PhD,4 Brent Blumenstein, PhD,5 Cindy Jacobs, PhD, MD4
- Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA
- University of California San Francisco, San Francisco, CA, USA
- Stanford University, Stanford, CA, USA
- Achieve Life Sciences, Seattle,WA, USA
- Trial Architecture Consulting, Chevy Chase, MD, USA
SGIM Annual Meeting, May 17, 2024
Funding
- NIH/NIDA (#R44-DA054784)
- Achieve Life Sciences (manufacturer of cytisinicline).
2
Author Disclosures
Rigotti | Consultant, research grant - Achieve Life Sciences |
Benowitz | Consultant - Achieve Life Sciences and other pharmaceutical |
companies about smoking cessation medications; Expert witness in | |
litigation against tobacco companies | |
Prochaska | Consultant - Achieve Life Sciences and mobile health technology |
companies; Expert witness in litigation against tobacco companies | |
Blumenstein | Statistical consultant - Achieve Life Sciences |
Cain, Ball, Jacobs, Clarke | Employees - Achieve Life Sciences |
3
Background: Cytisine
- Plant-basedalkaloid - Golden Rain (Cytisus laburnum) native to Europe
- Mechanism similar to varenicline
- Partial agonist at α4β2 nicotinic acetylcholine receptors.
- Smoking cessation aid used in Eastern and Central Europe for decades with evidence of efficacy (vs. placebo1 or NRT2)
- Achieve Life Sciences is developing it for smoking cessation in U.S.
- Cytisine → cytisinicline (new generic name)
o Effective and well tolerated in 2 U.S. Phase 3 RCTs3
1 West R et al. NEJM 2011;365:1193. 2 Walker N et al. NEJM 2014; 371:2353. | Golden Rain |
3 Rigotti NA et al. JAMA. 2023;330:152 and www.achievelifesciences.com | (Cytisus laburnum) |
Background: Vaping Cessation
- Can cytisinicline effectively treat other forms of nicotine addiction?
- Increasingly, people who use nicotine e-cigarettes ("vape") seek help to stop.
- Little evidence exists to guide treatment, especially pharmacological treatment.
- Varenicline was effective in one RCT.*
- In the U.S., no medication is FDA-approved for vaping cessation.
*Caponnetto P, et al. eClinicalMedicine, December 2023
ORCA V1: Phase 2 Randomized Clinical Trial
- AIM: Compare the efficacy and safety of 12 weeks of the new cytisinicline regimen (3 mg TID) vs. placebo, both with behavioral support, for vaping cessation
- STUDY DESIGN
- Double-blindRCT
- Sample size goal: n=150 o 2:1- cytisinicline: placebo
o All take one pill TID x12 weeks o All: regular behavioral support o All followed for16 weeks
Inclusion Criteria
- Age ≥18 years
- Daily use of a nicotine-containinge-cigarette (but no currentcigarette smoking)
- Baseline saliva cotinine >30 ng/mL AND expired air CO <10ppm
- Seek to stop vaping
- Agree to set quit date within 7-14 days of starting treatment
- Willing to participate in weekly behavioral support
- Medically and psychiatrically stable
- Negative urinary screen for drugs of abuse
Outcomes
- Primary Outcome
- Biochemically verified continuous abstinence (cotinine <10ng/mL) during each of the last 4 weeks of treatment (weeks 9-12)
- Secondary Outcomes
- Continuous abstinence from last 4 weeks of treatment to 4 weeks post-treatment (weeks 9-16)
- Past 7-day point prevalence e-cigarette vaping abstinence
- Safety
- Adverse events, serious adverse events (#, severity, and attributability to study drug)
- Analysis
- Intent to treat. Assume that missing data = participant is vaping.
PARTICIPATING SITES (N=5)
Enrollment
July - November 2022
Data collection ended
February 2023
CONSORT Diagram
231 Screened
160 Randomized
71 Not Randomized
160 randomized (2:1 ratio)
Stratified by history of smoking
107 Cytisinicline
(106 treated)
91 Followed for 12 weeks | (85%) |
77 Completed Treatment
30 Discontinued Treatment
89 Completed 16-Week Study (83%)
18 Did Not Complete Study
107 Analyzed (Efficacy)
106 Analyzed (Safety)
53 Placebo
(53 treated)
44 Followed for 12 weeks | (83%) |
40 Completed Treatment
13 Discontinued Treatment
42 Completed 16-Week Study (79%)
11 Did Not Complete Study
53 Analyzed
(Efficacy and Safety)
84% completed12 weeks
82% completed16 weeks
Intention-to-treat analysis
Attachments
- Original Link
- Original Document
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Disclaimer
Achieve Life Sciences Inc. published this content on 17 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 17 May 2024 20:24:14 UTC.
